Study Sheds Light on Aspirin’s Effects in Chronic Kidney Disease, but Questions Remain

For people with chronic kidney disease (CKD), daily low-dose aspirin use doesn’t appear to confer either primary or secondary cardiovascular benefit. On the other hand, it also doesn’t seem to accelerate kidney disease progression or cause major bleeding.

Those findings, from a new retrospective analysis of clinical trial data by Cleveland Clinic researchers, help to fill in the knowledge gaps when it comes to cardiovascular treatment in patients with chronic kidney disease, and provide some reassurance regarding the safety of aspirin in this population. But, many clinical questions remain.

Kidney disease is an independent risk factor for cardiovascular disease (CVD), says lead author Jonathan J. Taliercio, DO, FASN, Program Director of the Nephrology and Hypertension Fellowship and Assistant Professor of Medicine at the Cleveland Clinic Lerner College of Medicine.

“Approximately 37 million people in the United States, roughly 15% of the population, have chronic kidney disease. Most will never progress to kidney failure, but instead will die of heart disease. Yet, these individuals have been underrepresented in clinical trials so we don’t know if aspirin use decreases their cardiovascular events such as stroke and heart attacks. It’s an enormous gap in our medical knowledge,” he says.

Aspirin inhibits platelet activation and is currently recommended in low doses as secondary prevention for people in the general population who have had a prior heart attack or known cardiovascular disease and are therefore at increased risk for a future cardiovascular event. However, because aspirin can also lead to bleeding, medical groups now recommend against its use as primary cardiovascular prevention for most of the general population.

And for the time being, the new retrospective, non-randomized data aren’t sufficient to change that same clinical guidance to use daily low-dose aspirin in people with CKD who have already had a heart attack despite the negative finding, Dr. Taliercio cautions.

“For now, we need to continue to offer aspirin to our CKD patients for secondary prevention. And for primary, our findings align with previous studies in the general population. I wouldn’t advise changing the guidance for people with chronic kidney disease until we have randomized clinical trial data.”

Such data are anticipated from The Aspirin to Prevent a First Heart Attack or Stroke in People with Chronic Kidney Disease (ATTACK) study, which is currently recruiting 25,210 participants in the United Kingdom. Results are expected in 2025.

No benefit of low-dose aspirin found in people with CKD

The new findings come from the Chronic Renal Insufficiency Cohort (CRIC) Study, which enrolled 3,939 adults who had estimated glomerular filtration rates (eGFR) of 20-70 ml/min per 1.73m2 (Stage 3-4 kidney disease), from seven clinical centers throughout the United States. The major aims of the CRIC study are to examine the determinants of CKD progression, CVD, and mortality.

Dr. Taliercio, the CRIC principal investigator for the Cleveland Clinic study site, used the CRIC data to take a deep dive into the aspirin question. Prior data suggest aspirin may have unique effects, both negative and positive, in people with CKD. “Patients with kidney disease have contradictory bleeding risks – some bleed more while others clot more. That’s why aspirin can be great in one individual to combat clotting while it can worsen pre-existing bleeding in another,” he says.

Among the 3,664 CRIC subjects included in the analysis, 70.4% had no pre-existing cardiovascular disease and were considered the “primary prevention” cohort. Of those 2,578 individuals, 33.7% (870) were taking daily aspirin and 66.3% (1,708) were not. Among 1,086 who did have pre-existing cardiovascular disease, i.e., the “secondary prevention” group, 60.9% (661) were taking aspirin and 39.1% (425) were not.

A study limitation, Dr. Taliercio notes, is the lack of information about why they were or were not taking the aspirin, the exact dosage of the aspirin (full dose or baby aspirin), and whether it had been prescribed or not.

After adjustment for baseline differences among the groups including age, gender, comorbidities, and use of other medications, aspirin use wasn’t associated with overall mortality in either the primary prevention (hazard ratio 0.84, P = 0.06) or the secondary prevention (0.88, P = 0.08) groups.

Aspirin also had no influence on cardiovascular mortality in either the primary (1.12, P = 0.56) or secondary prevention (0.95, P = 0.67) groups.

Similarly, there was no effect of aspirin on a composite outcome of CVD events including myocardial infarction, stroke and peripheral arterial disease in either the primary (0.97, P = 0.79) or secondary prevention (1.08, P = 0.46) groups, nor in any of those individual endpoints in either group.

On the other hand, no harm seen either

While no CVD benefits of daily low-dose aspirin were identified for patients with chronic kidney disease, no harms were found either. Aspirin use wasn’t associated with dialysis or kidney transplant in the primary (0.95, P = 0.53) or secondary prevention (0.99, P = 0.91) groups.

“So if you’re concerned that prescribing aspirin in a person who really needs it for secondary cardiovascular prevention is going to worsen their kidney function, this didn’t show that,” Dr. Taliercio says.

As for major bleeding, the biggest concern with long-term aspirin use, there was also no effect in the primary (0.84, P = 0.27) or secondary (0.76, P = 0.05). prevention groups.

However, says Dr. Taliercio, “We tried to make the groups as similar as possible, but at the end of the day it’s not a randomized controlled trial. In any of these studies you could be missing things. Hopefully ATTACK will clarify. I think we’re all waiting for that.”

The current study findings were published in Kidney Medicine. Dr. Taliercio also presented them on November 3, 2022 at an American Society of Nephrology’s Kidney Week meeting.